Bottom Line:
HO-1 induction had no effect in control animals, but significantly decreased MAP in TNF-α-infused animals (108 ± 2 mmHg).Taken together, these data suggest that one of the key mechanisms by which HO exerts cytoprotective actions in the placenta during inflammation due to chronic ischemia is through suppression of sFlt-1.Further work elucidating the bioactive metabolites of HO-1 in innate inflammatory responses to placental ischemia is warranted.

Figure 2: (A) In response to TNF-α infusion, mean arterial pressure was significantly elevated compared to normal pregnant controls. Administration of CoPP had no significant effect on mean pressure in normal pregnant animals, but significantly reduced the mean pressure in animals infused with TNF-α. There was no significant effect of either TNF-α infusion or CoPP treatment on either fetal weight (B) or placental mass (C). Statistical significance at p < 0.05 is indicated by connecting lines. Level of significance is indicated by asterisks (*p < 0.05, **p < 0.005).

Mentions:
After 5 days of continuous infusion of TNF-α (Figure 2A), pregnant dams exhibited a significant 15-mmHg increase (104 ± 3 vs. 119 ± 3 mmHg, p < 0.005) in mean arterial pressure (MAP). While administration of the HO-1 inducer CoPP had no effect on control animals (104 ± 3 vs. 105 ± 3 mmHg), it significantly attenuated the rise in blood pressure caused by infusion of TNF-α (119 ± 3 vs. 108 ± 2 mmHg, p < 0.05). These data suggest that induction of HO-1 has no effect on blood pressure under normal conditions in pregnant rats, but blocks the hypertensive effects of TNF-α during pregnancy. In line with other published data in pregnant rodents, there was no effect of HO-1 induction on either fetal or placental mass (Figures 2B,C).

Figure 2: (A) In response to TNF-α infusion, mean arterial pressure was significantly elevated compared to normal pregnant controls. Administration of CoPP had no significant effect on mean pressure in normal pregnant animals, but significantly reduced the mean pressure in animals infused with TNF-α. There was no significant effect of either TNF-α infusion or CoPP treatment on either fetal weight (B) or placental mass (C). Statistical significance at p < 0.05 is indicated by connecting lines. Level of significance is indicated by asterisks (*p < 0.05, **p < 0.005).

Mentions:
After 5 days of continuous infusion of TNF-α (Figure 2A), pregnant dams exhibited a significant 15-mmHg increase (104 ± 3 vs. 119 ± 3 mmHg, p < 0.005) in mean arterial pressure (MAP). While administration of the HO-1 inducer CoPP had no effect on control animals (104 ± 3 vs. 105 ± 3 mmHg), it significantly attenuated the rise in blood pressure caused by infusion of TNF-α (119 ± 3 vs. 108 ± 2 mmHg, p < 0.05). These data suggest that induction of HO-1 has no effect on blood pressure under normal conditions in pregnant rats, but blocks the hypertensive effects of TNF-α during pregnancy. In line with other published data in pregnant rodents, there was no effect of HO-1 induction on either fetal or placental mass (Figures 2B,C).

Bottom Line:
HO-1 induction had no effect in control animals, but significantly decreased MAP in TNF-α-infused animals (108 ± 2 mmHg).Taken together, these data suggest that one of the key mechanisms by which HO exerts cytoprotective actions in the placenta during inflammation due to chronic ischemia is through suppression of sFlt-1.Further work elucidating the bioactive metabolites of HO-1 in innate inflammatory responses to placental ischemia is warranted.